Morin hydrate ameliorates cisplatin-induced ER stress, inflammation and autophagy in HEK-293 cells and mice kidney via PARP-1 regulation.

Int Immunopharmacol 2018 Mar 3;56:156-167. Epub 2018 Feb 3.

Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Republic of Korea. Electronic address:

The present study assessed the possible therapeutic potential of a natural flavonoid morin hydrate (MH), against cisplatin (CP) induced toxicity in HEK-293 cells and mice kidney. Herein, we observed that exposure of HEK-293 cells to CP (20 μM, 24 h) reduced the cell viability, and increased the intracellular ROS generation, nuclear DNA damage, Ca release, and accumulation of acidic vacuoles. Concomitantly, acute exposure of CP (30 mg/kg, 72 h) to male ICR mice induced histopathological changes in kidney tissue, and alterations in serum creatinine and blood urea nitrogen (BUN) levels. Oxidative stress mediated ER-stress was evidenced by the reduced expression of antioxidant enzymes such as SOD-1, SOD-2, GR, and Trx, and increased expression levels of CytP450, IRE1-α, PERK, and CHOP. The expression levels of major inflammatory response markers such as NF-κB, TNF-α, IL-1β, COX-2 and iNOS were significantly increased in the HEK-293 cells and mice kidney. Temporal up-regulation of p-AMPK and LC3I/II, and down regulation of mTOR was also noticed after CP treatment. CP-induced DNA damage led to activation of PARP-1, which plays a crucial role in inflammation, apoptosis and autophagy activation. Concurrently, co-treatment of CP-MH and CP-ANI (PARP-1 inhibitor) significantly attenuated the expression level of PARP-1, reduced cellular death, alleviated inflammatory responses, and inhibited autophagy stimulation in HEK-293 cells and mice kidney. On the basis of above findings, we suggest MH as a potential therapeutic agent against CP-induced nephrotoxicity.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2018.01.031DOI Listing
March 2018
15 Reads
2.472 Impact Factor

Publication Analysis

Top Keywords

hek-293 cells
20
mice kidney
16
cells mice
16
dna damage
8
expression levels
8
morin hydrate
8
cells
5
kidney
5
hek-293
5
mice
5
co-treatment cp-mh
4
levels oxidative
4
oxidative stress
4
enzymes sod-1
4
bun levels
4
cp-mh cp-ani
4
urea nitrogen
4
nitrogen bun
4
stress mediated
4
mediated er-stress
4

Similar Publications